A Phase I, Open-label, Multicentre, Dose Escalation Study to Assess the Safety and Tolerability, and Pharmacokinetics of AZD1480 in Asian Patients With Advanced Solid Malignancies and Asian Patients With Child-Pugh A to B7 Advanced Hepatocellular Carcinoma (HCC) in the Escalation Phase, Estimated Glomerular Filtration Rate(EGFR) or ROS Mutant NSCLC and Non-smokers With Lung Metastasis and Gastric Cancer and Solid Tumour With Biopsy Available in the Expansion Phase.
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- AstraZeneca
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- To investigate the safety and tolerability of AZD1480
研究概览
简要总结
This is Phase I, open-label and dose escalation study to evaluate the safety and tolerability of AZD1480(JAK2 inhibitor) in Asian patients with advanced solid tumors (Part A and C) and in patients with advanced HCC (Part B) in the escalation phase, EGFR or ROS mutant NSCLC and non-smokers with lung metastasis and gastric cancer in the expansion phase and to evaluate daily and BID dosing.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female aged 18 years or older
- •For Part A and C: Histological or cytological confirmation of a solid malignant tumour refractory to standard therapies or for which no standard therapies exist. Patients with lymphoma & HCC are excluded.
- •For Expansion : Histological or cytological confirmation of
- •Expansion 1: EGFR and/or ROS mutant NSCLC or Non-smokers with lung metastasis
- •Expansion 2: Gastric cancer or solid tumour with biopsy available (consenting paired biopsies)refractory to standard therapies or for which no standard therapies exist. Patients with lymphoma & HCC are excluded.
- •For Part B : Advanced or metastatic HCC, unresectable and incurable with ablative therapy or TACE, with no standard therapy available.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1 with no deterioration over the previous 2 weeks
- •For Part B : Child-Pugh liver function status classified as A to B7
排除标准
- •For any other chemotherapy, immunotherapy or anticancer agents, within 5 half lives or 3 weeks must have elapsed from treatment to of the first dose of investigational product, whichever is shorter.
- •With the exception of alopecia, any unresolved toxicities from prior therapy ≥ Grade 2 of CTCAE V4.02 at the time of starting study (except LFTs for HCC patients, which may be Grade 2 at the time of starting the study)
- •Any of the following conditions:Interferon treatment for HBV and HCV Prior Liver Transplantation
- •Inadequate bone marrow reserve or organ function as demonstrated by laboratory values
- •Evidence of established interstitial lung disease(ILD) on baseline high resolution computerized tomography(HRCT)
研究组 & 干预措施
Part A
Daily dosing of AZD1480 to the patients with solid tumours excluding HCC
干预措施: AZD1480 Daily (Drug)
Part B
BID dosing of AZD1480 to the patients with advanced HCC (Child-Pugh A to B7)
干预措施: AZD1480 BID (Drug)
Part C
BID dosing of AZD1480 to the patients with solid tumours excluding HCC
干预措施: AZD1480 BID (Drug)
Expansion
BID dosing of AZD1480 to the patients with EGFR or ROS mutant NSCLC and non-smokers with lung metastasis and gastric cancer and solid tumour with biopsy available.
干预措施: AZD1480 BID (Drug)
结局指标
主要结局
To investigate the safety and tolerability of AZD1480
时间窗: Safety and tolerability monitoring will proceed for whole study period. Screening, Cycle1Day1, Cycle1Day5 (only for Part B), Cycle1Day8, Cycle1Day15, Cycle2Day1, Cycle2Day8 and Day1 of further Cycles, IP discontinued visit and 30-days follow up
次要结局
- To evaluate the pharmacokinetics (PK) of AZD1480 following single dose and multiple doses(Part A and Expansion - 12 times during Cycle 1, 11 times during Cycle 2. Part B and C - 11 times during Cycle 1, 10 times during Cycle 2. *1 additional PK sample in Cycle 1 will be collect for optional biopsy sample collected patients.)
- To obtain a preliminary assessment of the anti-tumour activity of AZD1480(Tumour response assessment by RECIST (Response Evaluation Criteria In Solid Tumors) version 1.1 every 6 weeks)